Abstract Endocrine therapies, such as tamoxifen and aromatase inhibitors (AIs), are widely used in the clinic for treating hormone-sensitive early-stage breast cancer. These therapies are proven to reduce recurrence and death from breast cancer. However, not every patient will benefit from taking tamoxifen/AIs. There are substantial side effects associated with tamoxifen and AIs and as a result, patients' adherences to endocrine therapy are low. This highlights the crucial need for an early response marker for measuring the clinical efficacy (e.g., reduce breast cancer recurrence) of tamoxifen/AIs so that only women who are likely to benefit from the treatment will be subjected to the associated side effects. Several studies have shown mammographic breast density is associated with tamoxifen/AI use. The goal of this study is to perform a clinical evaluation of automated breast density assessment for translational use to monitor the effectiveness of adjuvant tamoxifen/AI therapy in predicting breast cancer recurrence. Our retrospective study is innovative in terms of using standard of care digital mammogram images to evaluate automated breast density assessment for translational/clinical use. The results of this study will provide to the clinic a clinical imaging-based early response biomarker that is reproducible, low-cost, and based on standard of care breast images, allowing personalized evaluation on the effects of adjuvant endocrine therapy.